Methods for inhibiting heterotopic ossification

Abstract

Methods of protecting muscle tissue from heterotopic ossification employ targeted deliveries of a neuromuscular inhibitor. A method of protecting muscle tissue from heterotopic ossification includes identifying a volume of muscle tissue that is susceptible to heterotopic ossification. A first aliquot of a therapeutic dose of a neuromuscular inhibitor is delivered at a first delivery site within the volume of muscle tissue. A second aliquot of the therapeutic dose is delivered at a second delivery site within the volume of muscle tissue. The first and second delivery sites are separated by a distance to distribute the therapeutic dose within the targeted volume of muscle tissue.

What is claimed is: 
     
       1. A method of protecting a targeted volume of muscle tissue from heterotopic ossification (HO), the method comprising:
 identifying the targeted volume, within a larger volume of muscle tissue, that is susceptible to HO; 
 delivering a first aliquot of a therapeutic dose of a neuromuscular inhibitor at a first delivery site within the targeted volume susceptible to HO; and 
 delivering a second aliquot of the therapeutic dose of the neuromuscular inhibitor at a second delivery site within the targeted volume at a first distance from the first delivery, wherein delivering the first and second aliquots separated by the first distance distributes the therapeutic dose within the targeted volume to reduce a required amount of the therapeutic dose for inhibiting HO, such that the therapeutic dose provides a protective concentration of the therapeutic dose that is sufficient to prevent formation of an HO lesion within the targeted volume, but insufficient to induce paralysis of the larger volume of muscle tissue. 
 
     
     
       2. The method of  claim 1 , wherein the neuromuscular inhibitor comprises at least one of Botulinum toxin type A, Botulinum toxin type B, Abobotulinum toxin A, or Incobotulinum toxin A. 
     
     
       3. The method of  claim 1 , wherein the neuromuscular inhibitor comprises at least one of a non-steroidal anti-inflammatory agent (NSAID), a COX-2 inhibitor, or a nuclear retinoic acid receptor gamma (RARγ) agonist. 
     
     
       4. The method of  claim 1 , further comprising:
 with a delivery device assembly comprising:
 an injector body having a shaped surface configured for complimenting a shape of the muscle volume susceptible to HO; and 
 a plurality of needles connected with the injector body and sized to penetrate to an intramuscular depth, wherein the injector body and the plurality of needles are operably connected such that the plurality of needles can distribute injection of the neuromuscular inhibitor into the targeted volume; 
 
 placing the shaped surface of the delivery device assembly against patient tissue proximate to the targeted volume such that dispensing ends of the plurality of needles penetrate through the patient tissue and extend into the targeted volume in at least two locations corresponding to the first and second delivery sites, wherein delivering the first aliquot of the therapeutic dose of the neuromuscular inhibitor comprises ejecting the first aliquot from a first needle of the plurality of needles at the first delivery site, and delivering the second aliquot of the therapeutic dose of the neuromuscular inhibitor comprises ejecting the second aliquot from a second needle of the plurality of needles at the second delivery site. 
 
     
     
       5. The method of  claim 4 , further comprising:
 scanning the targeted volume susceptible to HO with a scanning element; 
 determining based in part on the scanning, that the plurality of needles is correctly inserted into the targeted volume. 
 
     
     
       6. The method of  claim 1 , further comprising:
 with an injection guide having a plurality of guide holes arranged in an array, the injection guide having a shaped guide surface configured for complimenting a shape of the targeted volume susceptible to HO; 
 placing the injection guide against patient tissue proximate to the targeted volume; 
 inserting a first injection needle through a first guide hole of the injection guide, such that the first injection needle penetrates the targeted volume; and 
 inserting a second injection needle through a second guide hole of the injection guide, such that the second injection needle penetrates the muscle volume susceptible to HO targeted volume, wherein:
 delivering the first aliquot comprises ejecting the first aliquot from the first injection needle, and 
 delivering the second aliquot comprises ejecting the second aliquot from the second injection needle, wherein the first and second needle can be the same needle or different needles. 
 
 
     
     
       7. The method of  claim 1 , wherein identifying the targeted volume comprises predicting a site where a heterotopic ossification lesion may form in response to a trauma based on a location of the trauma. 
     
     
       8. The method of  claim 1 , wherein identifying the targeted volume comprises identifying a volume of muscle tissue in a joint where a heterotopic ossification lesion has a likelihood of formation and where the lesion would impinge motion of the flexure of the joint based on a location of the joint or based on a location of a trauma associated with the joint. 
     
     
       9. The method of  claim 1 , wherein identifying the targeted volume comprises identifying a volume of tissue proximate to an amputated limb, the volume of tissue being at least partially load-bearing when the amputated limb is fitted with a prosthesis. 
     
     
       10. The method of  claim 1 , wherein:
 the first delivery site and the second delivery site are positioned at respective first and second depths along a single needle path in the targeted volume, the first and second depths being different and separated along the needle path by the first distance; and 
 the first and second aliquots are delivered to the first and second delivery sites by sequentially injecting the first aliquot from a needle at the first depth, and injecting the second aliquot from the needle at the second depth. 
 
     
     
       11. The method of  claim 1 , further comprising:
 with an injection guide having one or more guide holes and a shaped guide surface configured to compliment a shape of a muscle volume susceptible to HO, placing the injection guide against patient tissue proximate to the targeted volume; 
 placing a spacer adjacent the injection guide and aligned with the one or more guide holes to adjust a relative thickness of the injection guide; 
 passing a first injection needle through the spacer and the injection guide prior to delivering the first aliquot; and 
 passing a second injection needle through the injection guide without the spacer prior to delivering the second aliquot. 
 
     
     
       12. The method of  claim 1 , further comprising:
 aligning an injection guide comprising a body and a plurality of guide holes with the identified target volume; 
 delivering the first aliquot through a first guide hole of the plurality of guide holes; and 
 delivering the second aliquot through a second guide hole of the plurality of guide holes that is different from the first guide hole. 
 
     
     
       13. The method of  claim 12 , wherein the first aliquot and the second aliquot are delivered simultaneously via first and second needles placed, respectively, through the first and second guide holes. 
     
     
       14. The method of  claim 12 , wherein the first aliquot and the second aliquot are delivered sequentially via one or more needles placed through the first and second guide holes. 
     
     
       15. The method of  claim 12 , wherein a first depth of the injection guide at the first guide hole is different from a second depth of the injection guide at the second guide hole, the first and second depths configured to control a penetration depth of a needle passed through either the first guide hole or the second guide hole. 
     
     
       16. The method of  claim 1 , further comprising delivering a plurality of aliquots of the neuromuscular inhibitor, including the first and second aliquots, the plurality of aliquots being spaced such that the therapeutic dose is distributed evenly throughout the muscle volume. 
     
     
       17. The method of  claim 1 , wherein the first aliquot is delivered to a first depth and the second aliquot is delivered to a second depth that is different than the first depth. 
     
     
       18. The method of  claim 1 , further comprising:
 delivering the first aliquot and the second aliquot via a needle of an automated injector. 
 
     
     
       19. The method of  claim 1 , wherein the therapeutic dose of the neuromuscular inhibitor prevents formation of the HO lesion by local inhibition of neuromuscular function within the targeted volume without inducing paralysis of the larger volume of muscle tissue.